New Aspects in the Diagnosis and Treatment of Hodgkin’s Disease PDF
Preview New Aspects in the Diagnosis and Treatment of Hodgkin’s Disease
Recent Results 117 in Cancer Research Managing Editors Ch. Herfarth, Heidelberg· H.-f. Senn, St. Gallen Associate Editors M. Baum, London· V Diehl, Kjjln E. Grundmann, Munster· F. Gutzwiller, Zurich W Hitzig, Zurich . M. F. Rajewsky, Essen M. Wannenmacher, Heidelberg Founding Editor P. Rentchnick, Geneva Recent Results in Cancer Research Volume 107 R. D. IsseIs, W. Wilmanns (Eds.): Application of Hyperthermia in the Treatment of Cancer 1988.118 figures, 56 tables. XII, 277. ISBN 3-540-18486-4 Volume 108 H.-J. Senn, A. Glaus, L. Schmid (Eds.): Supportive Care in Cancer Patients 1988.62 figures, 97 tables. XII, 342. ISBN 3-540-17150-9 Volume 109 W. Hinkelbein, G. Bruggmoser, R. Engelhardt (Eds.): Preclinical Hyperthermia 1988.182 figures, 40 tables. Xl, 261. ISBN 3-540-18487-2 Volume 110 P. Schlag, P. Hohenberger, U. Metzger (Eds.): Combined Modality Therapy of Gastrointestinal Tract Cancer 1988.105 figures, 122 tables. XVII, 301. ISBN 3-540-18610-7 Volume 111 H. Scheurlen, R. Kay, M. Baum (Eds.): Cancer Clinical Trials: A Critical Appraisal 1988.37 figures, 53 tables. Xl, 272. ISBN 3-540-19098-8 Volume 112 L. Schmid, H.-J. Senn (Eds.): AIDS-Related Neoplasias 1988.23 figures, 35 tables. IX, 97. ISBN 3-540-19227-1 Volume 113 U. Eppenberger, A. Goldhirsch (Eds.): Endocrine Therapy and Growth Regulation of Breast Cancer 1989.26 figures, 17 tables. IX, 92. ISBN 3-540-50456-7 Volume 114 P. Boyle, C. S. Muir, E. Grundmann (Eds.): Cancer Mapping 1989.89 figures, 64 tables. XI, 277. ISBN 3-540-50490-7 Volume 115 H.-J. Senn, A. Goldhirsch, R. D. Gelber, B. Osterwalder (Eds.): Adjuvant Therapy of Primary Breast Cancer 1989.65 figures, 94 tables. XVI, 296. ISBN 3-540-1881O-X Volume 116 K. W. Brunner, H. Fleisch, H.-J. Senn (Eds.): Bisphosphonates and Tumor Osteolysis 1989.22 figures, 6 tables. IX, 78. ISBN 3-540-50560-1 v. Diehl M. Pfreundschuh M. Loeffler (Eds.) New Aspects in the Diagnosis and Treatment of Hodgkin's Disease With 71 Figures and 91 Tables Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Professor Dr. med. Volker Diehl Professor Dr. med. Michael Pfreundschuh Dr. med. Dip!. Phys. Markus Loeffler I. Medizinische UniversiUitsklinik Kaln loseph-Stelzmann-Stra13e 9, 5000 Kaln 41, FRG ISBN-13: 978-3-642-83783-8 e-ISBN-13 :978-3-642-83781-4 DOl: 10.1007/978-3-642-83781-4 Library of Congress Cataloging-in-Publication Data New aspects in the diagnosis and treatment of Hodgkin's disease/V. Diehl, M. Pfreundschuh, M. Loeffler (eds.). p.cm.-(Recent results in cancer research: 117) Based on the First International Symposium on Hodgkin's Lymphoma in Cologne, Oct., 2-3, 1987. Includes Index. ISBN-I3:978-3-642-83783-8 (U. S.: alk. paper) 1. Hodgkin's disease-Congresses. I. Diehl, V. (Volker), 1938-. II. pfreundschuh, M. (Michael) III. Loeffler, M. (Markus), 1954-. IV. International Symposium on Hodgkin's Lymphoma (1st: 1987: Cologne, Germany) V. Series. [DNLM: 1. Hodgkin's Disease-diagnosis-congresses. 2. Hodgkin's Disease-therapy congresses. WI RE106P v. 117/WH 500 1987] RC261.R35 vol. 117 [RC644] 616.99'4 s-dc20 [616.99'446] DNLM/DLC 89-11302 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the Gennan Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1989 Softcover reprint of the hardcover 1st edition 1989 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in the book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. 2125/3140-543210 - Printed on acid-free paper. Preface In the field of Hodgkin's lymphoma, many new data have been collected during the last decade both on the cell of origin of this disease and on more effective therapies to cure the majority of pa tients even in the advanced stages. Therefore, it seems to be justi fied to compile these new data in a special volume of Recent Re sults in Cancer Research. This volume summarizes the contribu tions presented at the First International Symposium on Hodgkin's Disease that took place in Cologne (FRG) on October 2-3, 1988. There is little doubt that the Hodgkin and Reed-Sternberg (H and RS) cells and their variants represent the malignant population in Hodgkin's lymphoma; however, there is still a fierce debate as to the possible cell of origin of Hand RS cells. Many of the problems confounding earlier research into this question were related to the difficulty or virtual impossibility, of obtaining purified populations of Hand RS cells. Most of the recent progress stems from the establishment of permanent cell lines of Hand RS cells in culture. Though permanent cell lines may degenerate from their ancestors and may not be representative of the original cells, the data accu mulated demonstrate that the cells in vitro reflect very well the bio logical and immunological aspects of Hand RS cells in vivo. The marker spectrum of Hodgkin-derived cell lines in vitro and that of Hand RS cells in vivo, as well as gene rearrangement studies of the cell lines, suggest that Hand RS cells in vivo are lymphoid in origin. Even though gene rearrangement studies of biopsy material are not yet conclusive, immunological marker studies with mono clonal antibodies suggest that Hand RS cells are activated lym phoid cells of either T- or B-cell type. Taking into account the data presented and summarized in this volume, we cannot totally ex clude the derivation of Hand RS cells from other cells (e. g., mac rophages), especially in the light of some functional studies (e. g., antigen presentation) and the reactivity with monoclonal anti bodies that recognize antigens related to the monocytoid/myeloid VI Preface lineage. However, all contributors agree upon the conclusion that at the current state of our knowledge we must regard Hand RS cells as lymphoid. Just as revolutionary as the new data concerning the cell of ori gin in Hodgkin's lymphoma have been the changes in the diagnos tic and therapeutic approaches to this disease. The safest ground for diagnosing Hodgkin's disease is still conventional morphology, but immunohistology is of help in confirming the diagnosis, espe cially in cases which cannot be classified using morphological cri teria. Diagnostic laparotomy with splenectomy is no longer gener ally recommended. The new diagnostic strategies presented here - immunoscintigraphy and bone marrow scintigraphy with magnetic resonance imaging - may possibly help to replace this invasive method completely in the near future. The improvement of therapy in Hodgkin's lymphoma during the last two decades is mostly due to the development of effective combination chemotherapy protocols. More than 20 years after its inauguration, MOPP is still the golden standard by which all new chemotherapy protocols have to be measured. The gains accom plished by new drug combinations, if they exist at all, are minor if they are projected onto the total population of patients with Hodg kin's disease. With remission rates between 70% and 90% and cure rates less than 50%, the major challenge for clinical research of Hodgkin's lymphoma in the 1990s is the definition of prognostic subgroups by clinical or laboratory parameters in order to select patients who benefit from more aggressive therapy and those in whom the intensity, and thus the toxicity of treatment can be re duced. Oncologists dealing with adult patients are impressed by the re sults obtained in pediatric patients, which are presented here. Of course, the approaches used for children cannot simply be trans ferred to adult patients, but much can be learned from the tailoring of the diagnostic and therapeutic strategy to the individual pa tient's needs. The recent results of clinical trials demonstrate the value of risk factor analysis. It becomes evident that the staging system according to Ann Arbor may no longer serve as a strategy for making therapeutic decisions, and a more refined system of prognostic subgrouping is badly needed. The problem is that dif ferent risk factors were reported for different treatment strategies. To define intrinsic or therapy-independent risk factors, we need an intergroup analysis of risk factors. Such an analysis can only be ac complished by accumulating the data of several large international study groups. It is one of the most important results of the First In ternational Symposium on Hodgkin's Lymphoma that the participat ing representatives of the most important institutions and coopera tive groups have agreed to contribute their data for an internation al workshop on risk factor analysis which is now being carried out. Preface VII Failure of primary treatment need no longer be fatal. The thera peutic advances of conventional salvage therapy and the innova tive approach of bone marrow transplantation are discussed in a special section. Finally, the psychological problems that arise in treating our patients and the intermediate and long-term sequelae of treatment deserve further attention. These sequelae will answer the question whether our therapeutic efforts, which succeed in cur ing most of the patients, are really worthwhile. This can only be the case if we not only free the patients from their disease but also pro vide them with a psychological and somatic quality of life that jus tifies the efforts and the costs involved in conquering the disease. The attendance and the enthusiastic comments made us believe that the First International Symposium on Hodgkin's Lymphoma in Cologne succeeded in summarizing the most important goals that we have achieved during the last two decades and in defining the questions that remain to be answered in the future to complete our knowledge for the sake of the patients. I do not want to finish this preface without first thanking the Ministry of Research and Technology of the Federal Government (BMFT), The German Research Society (DFG), the Thyssen Foun dation, the Boehringer-Ingelheim Foundation, the German Asso ciation of Medical Oncology (Ala), and the City of Cologne for their financial and administrative support. My personal thanks go to our Hodgkin Study Group team, especially to Mrs. Nisters Backes and Olga Pavlovic and to our students, who guaranteed the flawless organization of a meeting that we hope many of the parti cipants will remember for a long time to come. Cologne, March 1989 For the editors Volker Diehl Contents Pathology and Cell Biology of Hodgkin's Disease 1 D. H. Wright Pathology of Hodgkin's Disease: Anything New? . 3 H. Stein, R. Schwarting, F. Dallenbach, and D. Dienemann Immunology of Hodgkin and Reed-Sternberg Cells .... 14 A. C. Feller and H. Griesser DNA Gene Rearrangement Studies in Hodgkin's Disease and Related Lymphomas: A Contribution to Their Cellular Origin. 27 C. Fonatsch, G. Gradl, and J. Rademacher Genetics of Hodgkin's Lymphoma. . . . . . . . . . . . . . .. 35 Hodgkin's Disease Derived Cell Lines. . . . . . . . . . . . . . . . .. 51 M. Schaadt, H. Burrichter, M. Pfreundschuh, E. Schell-Frederick, H. Tesch, C. Fonatsch, H. Stein, and V Diehl Biology of Hodgkin Cell Lines .................. . 53 D. B. Jones, A. J. W Furiey, J. Gerdes, M. F. Greaves, H. Stein, and D. H. Wright Phenotypic and Genotypic Analysis of Two Cell Lines Derived from Hodgkin's Disease Tissue Biopsies . . . . . . . . . . . . . . . . .. 62 S. Poppema, L. Visser, B. de Jong, M. Brinker, J. Atmosoerodjo, and W Timens The Typical Reed-Sternberg Phenotype and I g Gene Rearrangements of Hodgkin's Disease Derived Cell Line ZO Indicating a B-Cell Origin . . . . . . . . . . . . . . . . . . . . . 67 H. G. Drexler, S. M. Gignac, A. V HoJjbrand, B. F. Leber, J. Norton, M. S. Lok, and J. Minowada Characterization of Hodgkin's Disease Derived Cell Line HDLM-2. 75 X Contents H. Kamesaki, S. Fukuhara, H. Uchino, and T Nosaka A New Hypothesis on the Cellular Origin of Reed-Sternberg and Hodgkin Cells Based on the Immunological and Molecular Genetic Analysis of the KM-H2 Line. . . . . . . . . . . . . . . . . . . . .. 83 E. Paietta, R. J. Stockert, A. Morell, J. Racevskis, and P. H. Wiernik A Marker and Putative Pathoantigen of Hodgkin's Cells . . . . . .. 91 Development in Diagnostic Procedures. . . . . . . . . . . . . . . . .. 99 P. Carde, M. Pfreundschuh, L. da Costa, L. Manil, J. D. Lumbroso, B. Ca illou , C. Parmentier, J. C. Saccavini, and V. Diehl Radiolabeled Monoclonal Antibodies Against Reed-Sternberg Cells for in Vivo Imaging of Hodgkin's Disease by Immunoscintigraphy 101 H. Schicha, M. Franke, J. Smolorz, A. Linden, W Waters, and V. Diehl Diagnostic Strategies and Staging Procedures for Hodgkin's Lymphoma: Bone Marrow Scintigraphy and Magnetic Resonance Imaging .................................. 112 Therapeutic Strategies 121 Overviews. 123 H. Sack Radiotherapy Trials in Hodgkin's Disease 123 P. H. Wiernik Current Status of Chemotherapy for Hodgkin's Disease ....... 132 Report on Recent and Current Clinical Trials . .............. 142 M. Loeffler, M. Pfreundschuh, U. Ruhl, E. Hiller, H. Gerhartz, R. Roloff, M. Adler, W Schoppe, U. Hagen-Aukamp, G. Schmitt, J. Teichmann, V Brust, R. Fuchs, B. Makoski, H. Bartels, J. Entzian, G. Kuhn, A. Hellriegel, H. Kirchner, H. Emminger, G. Dolken, W Oertel, W Wilhelmy, B. Kruger, S. Petsch, H. f1luger, R. Hinterberger, P. Worst, W GajJmann, K. Smith, D. Hasenclever, and V. Diehl Risk Factor Adapted Treatment of Hodgkin's Lymphoma: Strategies and Perspectives. . . . . . . . . . . . . . . . . . . 142 M. Herold, G. Anger, K. Keinert, D. Hache, R. Kastner, and K. Wutke Reduced Combined Radiotherapy and Chemotherapy for Hodgkin's Disease - Risk-Adapted Treatment Approach ....... 163 Contents XI G. Bonadonna. P. Valagussa. A. Santoro. S. Viviani. V. Bonfante. and A. Banfi Hodgkin's Disease: The Milan Cancer Institute Experience with MOPP and ABVD ............................ 169 R. Somers. M. Tubiana. and M. Henry-Amar EORTC Lymphoma Cooperative Group Studies in Clinical Stage I-II Hodgkin's Disease - 1963 1987 . . . . . . . . . .. '" 175 R. T Hoppe. S. J. Horning. S. L. Hancock. and S. A. Rosenberg Current Stanford Clinical Trials for Hodgkin's Disease. . . . . 182 D. J. Straus. J. Gaynor. J. Myers. D. Merke. D. Chapman. J. Caravelli. L. Z. Nisce. B. J. Lee. and B. D. Clarkson Results and Prognostic Factors Following Optimal Treatment in Advanced Hodgkin's Disease ...................... 191 L. M. Fuller and F. B. Hagemeister Two Cycles of MOPP and Definitive Radiotherapy for Stage IlIA and III B Hodgkin's Disease. . . . . . . . . . . . . . . . . . . .. . 197 G. Schellong. I. Hornig. E. W Schwarze. and M. Wannenmacher Risk Factor Adapted Treatment of Hodgkin's Lymphoma in Childhood: Strategies and Results of Three Consecutive Multicenter Studies in the Federal Republic of Germany . . . . . . . . . . . . . . 205 J. Lemerle. O. Oberlin. G. Schaison. G. Leverger. D. Olive. M. Bonnet. D. Dufillot. and L. de Lumley Hodgkin's Disease in Children: Adaptation of Treatment to Risk Factors ................................... 214 Role of Bone Marrow Transplantation in the Treatment of Hodgkin's Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 M.J1reundschuh. M. Schaadt. and V. Diehl Conventional Salvage Therapy for Hodgkin's Lymphoma . 225 J. A. Spinolo. S. Jagannath. K. A. Dicke. K. E. Smith. F. Cabanillas. F. B. Hagemeister. L. J. Horwitz. P. McLaughlin. F. Swan. and G. Spitzer High-Dose Combination Chemotherapy with Cyclophosphamide, Carmustine, Etoposide, and Autologous Bone Marrow Transplantation in 60 Patients with Relapsed Hodgkin's Disease: The M. D. Anderson Experience .................... 233 A. M. Carella and A. M. Marmont Treatment of Resistant Hodgkin's Lymphoma with Bone Marrow Transplantation in Italy ......................... 239
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